This Program-Project encompasses a broad fundamental approach to the chemistry, biochemistry, and biology of tumor initiation and promotion due to chemicals. The objective of the Program-Project is a detailed knowledge of the processes involved in chemical carcinogenesis so that the stages at which controls can be imposed on the process can be identified and the human losses and disabilities from cancer can be reduced. The studies of Drs. J. and E. Miller are directed primarily toward a detailed knowledge of the matabolic activation of chemical carcinogens and of the reactions of the ultimate forms with tissue macromolecules that are involved in the initiation of carcinogenesis. Dr. Boutwell is examining the biochemical activities that are essential for the promotion of initiated cells, especially in mouse epidermis, so that gross tumors will develop. Dr. Pitot is studying the regulation of enzyme synthesis in normal, preneoplastic, and neoplastic liver cells and the possibility of defectiveness in the translational regulation of genetic expression as a mechanism of chemical carcinogenesis. Dr. Potter's primary interest is in the biochemical diversity of preneoplastic and neoplastic liver lesions induced by chemical carcinogens and in the characterization of the critical biochemical phenotype required for the progression of preneoplastic and minimally neoplastic liver to more malignant tumors.